Protective effects of gut originated Indolepropionic acid on testicular health through oxidative stress reduction and metabolic improvement in diabetic rats

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that induces significant oxidative damage to the male reproductive system. This study evaluates the protective effects of gut-derived Indolepropionic acid (IPA) against testicular damage in streptozotocin (STZ) induced T2DM rats. T2DM was induced in male rats with a high-fat diet and STZ (50 mg/kg). Groups included: Control, T2DM, T2DM + IPA, IPA only, and T2DM + Metformin, treated for four weeks. T2DM + IPA showed a significantly improved gonadosomatic index, healthier seminiferous tubules histology, characterised by the presence of spermatogonia and elongated spermatozoa and more viable sperm. T2DM + IPA also revealed reduced oxidative stress (elevated superoxide dismutase and catalase, lower malondialdehyde) and upregulated <i>KISS1</i> and <i>LDH-C</i> gene expressions while downregulated <i>FGF21</i>, compared to T2DM and T2DM + Metformin groups. These findings suggest IPA protects against diabetic testicular toxicity by enhancing antioxidant defences and modulating key metabolic and spermatogenic genes.